The overall objective of this proposal is to participate with the NICHD under a Cooperative Agreement Program in a multicenter cooperative clinical study comparing the safety and accuracy of chorionic villus sampling (CVS) in the first trimester of pregnancy with amniocentesis in the second trimester for the prenatal diagnosis of genetic disorders. Women in their first trimester of pregnancy will be recruited from the patient population at the Mount Sinai Medical Center, its affiliated hospitals, and the greater New York metropolitan area. Non-directive genetic counseling will be provided, and informed consent will be obtained. Participating patients will be randomized for CVS or amniocentesis. It is anticipated that 10 to 30 women per month will be randomized during Phase II and that 20 to 40 women per month will be randomized during Phase IIIa. CVS and amniocentesis will be performed with sonographic guidance. Specimens will be carefully prepared for cytogenetic and, when indicated, appropriate biochemical analyses. Efforts will be directed to determine the extent of maternal contamination and/or mosaicism in chorionic villi specimens analyzed directly and after culture. In addition, the physicokinetic properties of various enzymes will be compared in normal chorionic villi and amniocytes in order to identify differences which would provide inaccurate diagnostic results. Follow-up studies (Phases IIIb and IV) will include the confirmation of all CVS results by appropriate studies of cultured amniotic fluid cells obtained by amniocentesis, specimens from induced abortion material or specimens obtained from newborns monitored for indications other than advanced maternal age. Clinical evaluations will be performed on all monitored infants in the newborn nursery and at 6 months of age. In addition, cytogenetic and pathologic studies will be performed on spontaneous abortus material to identify cytogenetic abnormalities and/or malformations. The data from these studies, including the frequency of spontaneous abortions, will be collected for the multicenter analysis of the accuracy and safety of CVS vs. amniocentesis for prenatal diagnosis.